Individualizing the dosage of cancer chemotherapy can increase
survival rates for children with acute lymphoblastic leukemia (ALL)
without causing excessive toxicity, according to a study published in
the February 18, 1998, issue of The New England Journal of Medicine.
The study, conducted by cancer specialists at St. Jude Childrens
Research Hospital in Memphis, indicates that individualizing a
patients chemotherapy dosages based on drug elimination can
avoid low blood levels of anticancer medicines and thereby improve
outcomes for ALL--the most common form of childhood cancer, which
affects approximately 2,500 children in the United States each year.
Based on blood levels measured in each patient, clinicians adjusted
the amount of medications to avoid underdosing children with fast
elimination rates. This approach allows clinicians to optimize
dosages based on the patients individual requirements rather
than administering the same dosages to all children.
"In our study, patients who received individualized dosages had
significantly better outcomes than those treated with conventional
therapy," said William E. Evans, Pharmd, chairman of the
pharmaceutical sciences department at St. Jude Hospital and one of
the authors of the study.
"Our research proves that by giving different dosages to
patients based on how they process drugs--quickly or slowly--rather
than on body size, we can establish and maintain the level of
medication needed to more effectively treat this most common type of
leukemia," Evans said.
Rapid Drug Elimination, Not Drug Resistance, Causes Some Relapses
One of the important conclusions from this study is that with
conventional dosing of chemotherapy, some children relapse because
their body eliminates the medications too rapidly and not because
their leukemia is resistant to the chemotherapy.
The study was conducted with 182 children who were newly diagnosed
with ALL. The children were randomly assigned to one of two treatment
groups. One group received doses of chemotherapy drugs (methotrexate,
teniposide [Vumon], and cytarabine) based on body-surface area and
the other received dosages based on the rate at which they eliminate
these drugs. Patients in the individualized group received fewer
treatments at lower dosages and had better outcomes than patients who
were treated with the conventional approach.
"While individualizing dosage based on a patients ability
to eliminate drugs has been used with other types of medications such
as anti-seizure drugs, antibiotics and anti-asthma medications, this
is the first study to demonstrate that the individualized drug dosing
can be important for anticancer treatment," said Ching-Hon Pui,
MD, co-director with Dr. Evans of St. Jude Hospitals
hematological malignancies program.